Alprazoalm can be delivered via two methods. The first one being the immediate release mode. The immediate-release Alprazolam (XANAX® (Alprazolam)) can be prescribed for administration of up to four doses per day for treatment of anxiety and, in some instances, in excess of four doses per day for treatment of panic disorders disclosed in US 2004/0006072A1. However, such frequency of dosing is bothersome and can adversely affect patient stability. Further, breakthrough anxiety can be a problem in current dosing methods.
The non immediate-release delivery systems may be broadly divided into following categories. (Ref: Remington's Pharmaceutical Sciences, 18th Edition, Mack Publishing Company, Page 1677)                a) Delayed release: These release systems are those, which use repetitive, intermittent dosings of a drug from one or more immediate release units incorporated into a single dosage form. This release system provides a patient compliance, however, it does not produce or maintain uniform drug blood levels within the therapeutic range.        b) Site-Specific and receptor release: This release system refers to a targeting of a drug directly to a certain biological location.        c) Sustained-release: This system includes any drug delivery system that achieves slow release of drug-over an extended period of time. If the system is successful at maintaining constant drug levels in the blood or target tissue, it is considered a controlled-release system. If it is unsuccessful at this, but extends the duration of action over that achieved by conventional delivery, it is considered a prolonged release system.        
XANAX® (Alprazolam) tablet, which is an immediate release formulation of Alprazolam, are designated to be divided by the patient into equally sized portions for dose control as disclosed in Physicians Desk Reference, 58.sup.th edition (2004), pp 2798-2802. The immediate release tablet needs to be taken at frequent intervals. The shortcoming faced in the immediate release is maintaining the drug concentration in the blood level. As the drug level is not maintained, there exists peaks and trough phenomena. Further, once the drug level descends down, during the trough interval, the panic attacks during this interval might create problems as referred patent US 2004/0006072 A1. Moreover, the peak and trough delivery pattern provided by known dosage forms result in undesirable effects, such as sedation due to over dose of medication when reached at the peak point in the beginning, memory impairment and abuse potential.
The dividing of the dose is generally not appropriate for extended release dosage forms that are usually designed to administer as a while. However, there exists a shortcoming with the alprazolam extended-release dosage from i.e. a wide range of dosage amount is prescribable, depending upon the nature and the severity being treated. Further, certain treatment regimens require different dosage amounts to be administered on different days. Further extended release products contain a higher drug load and thus any loss of integrity of the release characteristics of the dosage forms has a potential problem
The release rate can also be altered by various factors including food and the rate of transit through the gut.
Hence, it would be of great benefit to provide a sustained release alprazolam formulation system that is adaptable to a broad range of dosage strengths, yet exhibits substantial bioequivalence, when different dosage strengths are administered in an equal total dosage amount. One approach to solve this problem would be to provide all dosage strengths in an identical formulation, wherein higher dosage strengths are accommodated in proportionally larger dosage units. However, it is found preferable to provide all dosage strengths in tablets of similar total weight. This facilitates the avoidance of excessively small tablets for the lower dosage strengths, and excessively large tablets for higher dosage strengths.
A good drug delivery system is expected to provide efficient delivery to target tissue, steady therapeutic concentrations and minimizing exposure to nontarget tissue. It is also possible to reduce the dose or frequency and to improve compliance. The systems can enhance the therapeutic ratio and regimens of many existing agents that would not be useful in conventional dosage forms because of their toxicity or short half-lives. In this manner, a drug treatment is achieved, whose criteria are (a) better efficacy, (b) selectivity and (c) safety.
Further, there remains a need for an effective dosage form that provides a release of alprazolam over a period of time, which would cause a reduction in side effects associated with alprazolam dosings.
Thus, a sustained-release formulation system for alprazolam is desired that accommodates dosage strengths over at least a six fold range from 0.5 mg to 3 mg in substantially the same total dosage form weight, yet exhibits bioequivalence over a corresponding range of excipient/drug weight ratios.
An approach to solve this problem would be to identify for a sustained-release dosage form utilizing an HPMC matrix, a suitable amount of mix of HPMC giving substantially equivalent in vivo release and absorption rates over a broad range of alprazolam loadings as referred in patent application US 20040006072. Though mentioned therein, the only exemplified total weight of HPMC is 121.2 mg, having 1:1 ratio only. Surprisingly, in our hand, we found that the in-vitro profile of the composition prepared according to US 2004/0006072 when compared with XANAX® (Alprazolam) XR, the Standard Deviation (SD) as well as % Relative Standard
Deviation (% RSD) showed substantially high figures. These substantially high figures relates to the high degree of fluctuations in the said composition comparative to XANAX® (Alprazolam) XR, thus creating a demand for providing a better sustained release composition.
Currently available alprazolam compositions do not provide the desired pharmaceutical effect. Hence, there is a need for providing better sustained release compositions.
The use of lower quantities of (a) K4M HPMC and (b) K100LVP HPMC gives comparatively better results with respect to drug release. Due to the same, there are less fluctuations in % related standard deviation. Hence, the pharmaceutical composition prepared according to the current invention is superior to the prior are compositions.
The dissolution profile in biological system is reflected from in-vitro dissolution results. It is advisable to have better pharmaceutical composition having less fluctuations, which are inturn dependent on the in-vitro dissolution profile. Thus, the pharmaceutical composition according to the current embodiment is advantageous and better for patients as compared to the prior art compositions.